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TGM2 (transglutaminase 2)

Written2013-11Lisa Dyer
Departments of Biochemistry, Molecular Biology, University of Florida, Gainesville, Florida, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesprotein-glutamine-gamma-glutamyltransferase
Alias_symbol (synonym)TGC
HGNC (Hugo) TGM2
LocusID (NCBI) 7052
Atlas_Id 44078
Location 20q11.23  [Link to chromosome band 20q11]
Location_base_pair Starts at 36756864 and ends at 36793700 bp from pter ( according to hg19-Feb_2009)  [Mapping TGM2.png]
Fusion genes
(updated 2016)
CNPPD1 (2q35) / TGM2 (20q11.23)PITPNM2 (12q24.31) / TGM2 (20q11.23)RTKN (2p13.1) / TGM2 (20q11.23)
SFMBT2 (10p14) / TGM2 (20q11.23)TAL1 (1p33) / TGM2 (20q11.23)TGM2 (20q11.23) / DAG1 (3p21.31)
TGM2 (20q11.23) / DDX17 (22q13.1)TGM2 (20q11.23) / TGM2 (20q11.23)

DNA/RNA

 
Description The gene encompasses 36838bp; 13 exons; a dense CpG island engulfs exon 1 and the transcriptional start site; negative strand.
Transcription Two transcript variants 1) 3937bp; 2) 2326bp (C-terminal truncation exons 11-13); induced by NFkB, retinoic acid, IL-6, TGF-beta1, HRE, AP-1 and GRE.

Protein

Description 687 amino acids; 78 kilodaltons; monomer.
Expression Ubiquitously expressed.
Localisation Mostly intracellular (cytosol, nucleus and cell membrane); extracellular.
Function Multifunctional enzyme with transglutaminase crosslinking activity (catalyze covalant bonds between the ε-amino group of a lysine and the γ-carboxyl group of a glutamine residue) stabilizing the extracellular matrix (ECM) and cell-ECM interaction; require Ca2+ for catalytic activity; inhibited by GTP; under stress (loss of Ca2+) may play a role in apoptosis; involved in wound healing and inflammation ; aberrent overexpression of TG2 is linked to chemotherapeutic drug resistance.

Mutations

Germinal No germinal mutations have been identified; low frequency of SNPs.
Somatic No somatic mutations have been identified in cancer; can be transcriptionally silenced by CpG methylation in cancer (breast and brain); overexpression in many cancers; 3 missense mutations identified in early-onset type 2 diabetes patients (c.989T>G, c.992T>A, c.998A>G).

Implicated in

Note
  
Entity Breast cancer
Oncogenesis Overexpression renders culture mammary epithelial cells resistant to doxorubicin, associated with invasive phenotype and epithelial-to-mesenchymal transition; epigenetic silencing has been documented in many breast cancer cell lines and patient samples; In 30 patients, TG2 overexpression was found more often in lymph node metastases than primary tumors.
  
  
Entity Ovarian cancer
Prognosis Overexpression of TG2 is associated with negative survival in 93 patients (p=0.007).
Oncogenesis Overexpression renders ovarian cancer cells resistant to cisplatin and is associated with higher tumor stage.
  
  
Entity Pancreatic cancer
Prognosis Overall survival of stage II pancreatic ductal adenocarcinoma (PDAC) patients with TG2-mediated loss of PTEN was poor (20.7 months) compared to 68.6 months for TG2 negative and PTEN positive patients.
Oncogenesis Overexpression; resistance to gemcitabine; in 51 PDAC tumor samples overexpression of TG2 was associated with loss of PTEN expression.
  
  
Entity Non-small cell lung cancer (NSCLC)
Prognosis In 429 Korean patients, TG2 expression was associated with shorter disease free survival and correlated with recurrence.
Oncogenesis Overexpression ; cisplatin resistance.
  
  
Entity Celiac disease
Note Autoantibodies against TG2 ; autoantibodies are deposited in the small-bowl mucosa; TG2 crosslinks gliadin peptides (gluten) derived.
  

Bibliography

The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer.
Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD.
Carcinogenesis. 2008 Mar;29(3):510-8. doi: 10.1093/carcin/bgm280. Epub 2008 Jan 3.
PMID 18174247
 
Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor k light chain enhancer of activated B cells (NFkB) signaling controls basal and DNA damage-induced transglutaminase 2 expression.
Ai L, Skehan RR, Saydi J, Lin T, Brown KD.
J Biol Chem. 2012 May 25;287(22):18330-41. doi: 10.1074/jbc.M112.339317. Epub 2012 Apr 4.
PMID 22493284
 
Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a putative mutation in a MODY patient.
Bernassola F, Federici M, Corazzari M, Terrinoni A, Hribal ML, De Laurenzi V, Ranalli M, Massa O, Sesti G, McLean WH, Citro G, Barbetti F, Melino G.
FASEB J. 2002 Sep;16(11):1371-8.
PMID 12205028
 
Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling.
Cao L, Petrusca DN, Satpathy M, Nakshatri H, Petrache I, Matei D.
Carcinogenesis. 2008 Oct;29(10):1893-900. doi: 10.1093/carcin/bgn158. Epub 2008 Jul 29.
PMID 18667446
 
Transglutaminase 2 as an independent prognostic marker for survival of patients with non-adenocarcinoma subtype of non-small cell lung cancer.
Choi CM, Jang SJ, Park SY, Choi YB, Jeong JH, Kim DS, Kim HK, Park KS, Nam BH, Kim HR; Korean Thoracic Oncology Research Group (KTORG), Kim SY, Hong KM.
Mol Cancer. 2011 Sep 24;10:119. doi: 10.1186/1476-4598-10-119.
PMID 21943122
 
Clinical and biological significance of tissue transglutaminase in ovarian carcinoma.
Hwang JY, Mangala LS, Fok JY, Lin YG, Merritt WM, Spannuth WA, Nick AM, Fiterman DJ, Vivas-Mejia PE, Deavers MT, Coleman RL, Lopez-Berestein G, Mehta K, Sood AK.
Cancer Res. 2008 Jul 15;68(14):5849-58. doi: 10.1158/0008-5472.CAN-07-6130.
PMID 18632639
 
Polymorphism of transglutaminase 2: unusually low frequency of genomic variants with deficient functions.
Kiraly R, Barta E, Fesus L.
Amino Acids. 2013 Jan;44(1):215-25. doi: 10.1007/s00726-011-1194-6. Epub 2011 Dec 13.
PMID 22160262
 
Transglutaminase 2-targeted autoantibodies in celiac disease: Pathogenetic players in addition to diagnostic tools?
Lindfors K, Maki M, Kaukinen K.
Autoimmun Rev. 2010 Sep;9(11):744-9. doi: 10.1016/j.autrev.2010.06.003. Epub 2010 Jun 12. (REVIEW)
PMID 20547248
 
Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer.
Mehta K, Fok J, Miller FR, Koul D, Sahin AA.
Clin Cancer Res. 2004 Dec 1;10(23):8068-76.
PMID 15585642
 
Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer.
Park KS, Kim HK, Lee JH, Choi YB, Park SY, Yang SH, Kim SY, Hong KM.
J Cancer Res Clin Oncol. 2010 Apr;136(4):493-502. doi: 10.1007/s00432-009-0681-6. Epub 2009 Sep 18.
PMID 19763620
 
Missense mutations in the TGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes. Mutation in brief no. 982. Online.
Porzio O, Massa O, Cunsolo V, Colombo C, Malaponti M, Bertuzzi F, Hansen T, Johansen A, Pedersen O, Meschi F, Terrinoni A, Melino G, Federici M, Decarlo N, Menicagli M, Campani D, Marchetti P, Ferdaoussi M, Froguel P, Federici G, Vaxillaire M, Barbetti F.
Hum Mutat. 2007 Nov;28(11):1150.
PMID 17939176
 
Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase.
Satpathy M, Cao L, Pincheira R, Emerson R, Bigsby R, Nakshatri H, Matei D.
Cancer Res. 2007 Aug 1;67(15):7194-202.
PMID 17671187
 
Epithelial-to-mesenchymal transition and ovarian tumor progression induced by tissue transglutaminase.
Shao M, Cao L, Shen C, Satpathy M, Chelladurai B, Bigsby RM, Nakshatri H, Matei D.
Cancer Res. 2009 Dec 15;69(24):9192-201. doi: 10.1158/0008-5472.CAN-09-1257.
PMID 19951993
 
Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer.
Verma A, Guha S, Diagaradjane P, Kunnumakkara AB, Sanguino AM, Lopez-Berestein G, Sood AK, Aggarwal BB, Krishnan S, Gelovani JG, Mehta K.
Clin Cancer Res. 2008 Apr 15;14(8):2476-83. doi: 10.1158/1078-0432.CCR-07-4529.
PMID 18413840
 
Tissue transglutaminase-mediated chemoresistance in cancer cells.
Verma A, Mehta K.
Drug Resist Updat. 2007 Aug-Oct;10(4-5):144-51. Epub 2007 Jul 27. (REVIEW)
PMID 17662645
 

Citation

This paper should be referenced as such :
Dyer, L
TGM2 (transglutaminase 2)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(6):397-399.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TGM2ID44078ch20q11.html


External links

Nomenclature
HGNC (Hugo)TGM2   11778
Cards
AtlasTGM2ID44078ch20q11
Entrez_Gene (NCBI)TGM2  7052  transglutaminase 2
AliasesG-ALPHA-h; GNAH; HEL-S-45; TG2; 
TGC
GeneCards (Weizmann)TGM2
Ensembl hg19 (Hinxton)ENSG00000198959 [Gene_View]  chr20:36756864-36793700 [Contig_View]  TGM2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000198959 [Gene_View]  chr20:36756864-36793700 [Contig_View]  TGM2 [Vega]
ICGC DataPortalENSG00000198959
TCGA cBioPortalTGM2
AceView (NCBI)TGM2
Genatlas (Paris)TGM2
WikiGenes7052
SOURCE (Princeton)TGM2
Genetics Home Reference (NIH)TGM2
Genomic and cartography
GoldenPath hg19 (UCSC)TGM2  -     chr20:36756864-36793700 -  20q12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TGM2  -     20q12   [Description]    (hg38-Dec_2013)
EnsemblTGM2 - 20q12 [CytoView hg19]  TGM2 - 20q12 [CytoView hg38]
Mapping of homologs : NCBITGM2 [Mapview hg19]  TGM2 [Mapview hg38]
OMIM190196   
Gene and transcription
Genbank (Entrez)AA493184 AF311286 AK058031 AK126508 AK291714
RefSeq transcript (Entrez)NM_004613 NM_198951
RefSeq genomic (Entrez)NC_000020 NC_018931 NT_011362 NW_004929418
Consensus coding sequences : CCDS (NCBI)TGM2
Cluster EST : UnigeneHs.517033 [ NCBI ]
CGAP (NCI)Hs.517033
Alternative Splicing GalleryENSG00000198959
Gene ExpressionTGM2 [ NCBI-GEO ]   TGM2 [ EBI - ARRAY_EXPRESS ]   TGM2 [ SEEK ]   TGM2 [ MEM ]
Gene Expression Viewer (FireBrowse)TGM2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7052
GTEX Portal (Tissue expression)TGM2
Protein : pattern, domain, 3D structure
UniProt/SwissProtP21980   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP21980  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP21980
Splice isoforms : SwissVarP21980
Catalytic activity : Enzyme2.3.2.13 [ Enzyme-Expasy ]   2.3.2.132.3.2.13 [ IntEnz-EBI ]   2.3.2.13 [ BRENDA ]   2.3.2.13 [ KEGG ]   
PhosPhoSitePlusP21980
Domaine pattern : Prosite (Expaxy)TRANSGLUTAMINASES (PS00547)   
Domains : Interpro (EBI)Gln_gamma-glutamylTfrase_euk    Ig-like_fold    Ig_E-set    Transglutaminase-like    Transglutaminase_C    Transglutaminase_CS    Transglutaminase_N   
Domain families : Pfam (Sanger)Transglut_C (PF00927)    Transglut_core (PF01841)    Transglut_N (PF00868)   
Domain families : Pfam (NCBI)pfam00927    pfam01841    pfam00868   
Domain families : Smart (EMBL)TGc (SM00460)  
Conserved Domain (NCBI)TGM2
DMDM Disease mutations7052
Blocks (Seattle)TGM2
PDB (SRS)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
PDB (PDBSum)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
PDB (IMB)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
PDB (RSDB)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
Structural Biology KnowledgeBase1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
SCOP (Structural Classification of Proteins)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
CATH (Classification of proteins structures)1FAU    1KV3    2Q3Z    3LY6    3S3J    3S3P    3S3S    4PYG   
SuperfamilyP21980
Human Protein AtlasENSG00000198959
Peptide AtlasP21980
HPRD01825
IPIIPI00294578   IPI00218251   IPI00218252   IPI01013460   IPI01013011   IPI00873556   
Protein Interaction databases
DIP (DOE-UCLA)P21980
IntAct (EBI)P21980
FunCoupENSG00000198959
BioGRIDTGM2
STRING (EMBL)TGM2
ZODIACTGM2
Ontologies - Pathways
QuickGOP21980
Ontology : AmiGOprotein-glutamine gamma-glutamyltransferase activity  protein-glutamine gamma-glutamyltransferase activity  protein binding  mitochondrion  endoplasmic reticulum  endoplasmic reticulum  cytosol  focal adhesion  phospholipase C-activating G-protein coupled receptor signaling pathway  peptide cross-linking  intrinsic component of plasma membrane  intrinsic component of plasma membrane  negative regulation of endoplasmic reticulum calcium ion concentration  positive regulation of apoptotic process  apoptotic cell clearance  positive regulation of cell adhesion  metal ion binding  positive regulation of mitochondrial calcium ion concentration  branching involved in salivary gland morphogenesis  salivary gland cavitation  extracellular exosome  
Ontology : EGO-EBIprotein-glutamine gamma-glutamyltransferase activity  protein-glutamine gamma-glutamyltransferase activity  protein binding  mitochondrion  endoplasmic reticulum  endoplasmic reticulum  cytosol  focal adhesion  phospholipase C-activating G-protein coupled receptor signaling pathway  peptide cross-linking  intrinsic component of plasma membrane  intrinsic component of plasma membrane  negative regulation of endoplasmic reticulum calcium ion concentration  positive regulation of apoptotic process  apoptotic cell clearance  positive regulation of cell adhesion  metal ion binding  positive regulation of mitochondrial calcium ion concentration  branching involved in salivary gland morphogenesis  salivary gland cavitation  extracellular exosome  
Pathways : BIOCARTAPhospholipase C d1 in phospholipid associated cell signaling [Genes]   
Pathways : KEGGHuntington's disease   
NDEx NetworkTGM2
Atlas of Cancer Signalling NetworkTGM2
Wikipedia pathwaysTGM2
Orthology - Evolution
OrthoDB7052
GeneTree (enSembl)ENSG00000198959
Phylogenetic Trees/Animal Genes : TreeFamTGM2
HOVERGENP21980
HOGENOMP21980
Homologs : HomoloGeneTGM2
Homology/Alignments : Family Browser (UCSC)TGM2
Gene fusions - Rearrangements
Fusion : MitelmanSFMBT2/TGM2 [10p14/20q11.23]  [t(10;20)(p14;q11)]  
Fusion: TCGASFMBT2 10p14 TGM2 20q11.23 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTGM2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TGM2
dbVarTGM2
ClinVarTGM2
1000_GenomesTGM2 
Exome Variant ServerTGM2
ExAC (Exome Aggregation Consortium)TGM2 (select the gene name)
Genetic variants : HAPMAP7052
Genomic Variants (DGV)TGM2 [DGVbeta]
DECIPHER (Syndromes)20:36756864-36793700  ENSG00000198959
CONAN: Copy Number AnalysisTGM2 
Mutations
ICGC Data PortalTGM2 
TCGA Data PortalTGM2 
Broad Tumor PortalTGM2
OASIS PortalTGM2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTGM2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTGM2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TGM2
DgiDB (Drug Gene Interaction Database)TGM2
DoCM (Curated mutations)TGM2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TGM2 (select a term)
intoGenTGM2
NCG5 (London)TGM2
Cancer3DTGM2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM190196   
Orphanet
MedgenTGM2
Genetic Testing Registry TGM2
NextProtP21980 [Medical]
TSGene7052
GENETestsTGM2
Huge Navigator TGM2 [HugePedia]
snp3D : Map Gene to Disease7052
BioCentury BCIQTGM2
ClinGenTGM2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7052
Chemical/Pharm GKB GenePA36491
Clinical trialTGM2
Miscellaneous
canSAR (ICR)TGM2 (select the gene name)
Probes
Litterature
PubMed333 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTGM2
EVEXTGM2
GoPubMedTGM2
iHOPTGM2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Feb 2 14:11:43 CET 2017

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